Fri Oct 28 2022

64 articles - From Friday Oct 21 2022 to Friday Oct 28 2022

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Guidelines

Guidelines, position statements, white papers, technical reviews, consensus statements, etc…

Ann Oncol

Management of toxicities from immunotherapy: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.

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Meta-analysis

meta-analyses and systematic reviews


Original articles

RCT, clinical trials, retrospective studies, etc…

Am J Hematol

Allogeneic hematopoietic cell transplantation in patients with CML chronic phase in the era of third generation tyrosine kinase inhibitors: a retrospective study by the Chronic Malignancies Working Party of the EBMT.

No difference in OS, PFS, RI or NRM was evident related to the number of TKI prior to allo-HCT or to the type of TKI (p=ns). Significant factors influencing OS and PFS were >CP1 vs CP1 and Karnofsky performance (KPS) score >80 vs =80, highlighting CP1 patients undergoing allo-HCT have improved survival compared to >CP1 and the importance of careful allo-HCT candidate selection.

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Impact of Academic Medical Center Access on Outcomes in Multiple Myeloma.

On this analysis, MM patients treated at ACs have significantly improved survival. While potentially related to access to specialized care, socioeconomic factors that drive facility selection may also contribute.

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Blood

How I Treat: Inpatient Consultations for Quantitative Neutrophil Abnormalities in Adults.

Neutropenia can arise from infection, medications, autoimmune destruction, sequestration, nutritional deficiency, malignancy, and congenital neutropenia syndromes. In the evaluation of al abnormalities of neutrophil number, the timing of the change and the patient's historical neutrophil count are crucial.

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Hypomorphic RAG deficiency: impact of disease burden on survival and thymic recovery argues for early diagnosis and HSCT.

Immune reconstitution, particularly recovery of naïve CD4+ T-cells was faster and more robust in patients transplanted before 3.5 years and without organ damage. These findings support the indication for early transplantation.

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IL-13/IL-4 signaling contributes to fibrotic progression of the myeloproliferative neoplasms.

Lastly, we found an increase in the numbers of marrow T cells and mast cells, which are known sources of IL-13. Together, our data demonstrate that IL-13 is involved in disease progression in MF and that inhibition of the IL-13/IL-4 signaling pathway might serve as a novel therapeutic target to treat MF.

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Venetoclax and idasanutlin in relapsed/refractory AML: a non-randomized, open-label phase 1b trial.

IDH1/2 and RUNX1 mutations were associated with venetoclax-idasanutlin sensitivity, even in some patients with co-occurring TP53 mutations; most emergent TP53 clones were pre-existing. Our findings will aid ongoing/future trials of BCL-2/MDM2 inhibitor combinations.

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Blood Adv

A Phase 2 Study of Nivolumab Combined with Ibrutinib in Patients with Diffuse Large B-cell Richter Transformation of CLL.

Given the limited treatment options for patients with RT, checkpoint inhibition provides a potential therapeutic option. This trial is registered at as NCT02420912.

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EVI1 exerts distinct roles in AML via ERG and cyclin D1 promoting a chemoresistance and immune-suppressive environment.

Overexpression of EVI1 and cyclin D1 was associated with interferon- signature and increased expression of chemokines, with increased exhaustion molecules in T cells also in human AML datasets. These data collectively suggest that ERG and cyclin D1 play pivotal roles in the biology of EVI1+ AML, where ERG forms aggressive disease nature and chemoresistance, and cyclin D1 leads to interferon- signature and exhausted T cell phenotypes, which could be potentially targeted.

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HDAC1 regulates the chromatin landscape to control transcriptional dependencies in chronic lymphocytic leukemia.

We focused on a specific set of microRNA genes and show that their upregulation was inversely correlated with the expression of CLL specific survival, transcription factor and signaling genes. Our findings identify that the transcriptional activator and repressor functions of HDACs cooperate within the same tumor to establish the transcriptional dependencies essential for survival in CLL.

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Health Following Recovery from Immune Thrombotic Thrombocytopenic Purpura: The Patient's Perspective.

Although hematologists pronounce patients as recovered, iTTP remains a life-changing event. Patients often did not return to their previous functioning; relationships and their careers were affected. However, patients may forget to discuss these concerns with their hematologist. To improve remission care, hematologists should incorporate patient-reported outcome measures evaluating these symptoms in remission visits.

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Orally bioavailable BTK PROTAC active against wild-type and C481 mutant BTKs in human lymphoma CDX mouse models.

UBX-382 also provoked the cell-type-dependent and selective degradation of cereblon (CRBN) neo-substrates in various hematological cancer cells. These results suggest that UBX-382 treatment is a promising therapeutic strategy for B-cell-related blood cancers with improved efficacy and diverse applicability.

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Pirtobrutinib Targets BTK C481S in Ibrutinib-Resistant CLL but Second-Site BTK Mutations Lead to Resistance.

At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability and cytokine production. We employed longitudinal whole exome sequencing on two patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to non-covalent BTKi.

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Safety and efficacy of atezolizumab with rituximab and CHOP in previously untreated diffuse large B-cell lymphoma.

One patient had a fatal AE (unconfirmed progressive multifocal leukoencephalopathy), that was considered related to atezolizumab and rituximab, and 17 (40.5%) patients experienced atezolizumab-related AEs of special interest. In previously untreated patients with DLBCL, atezo-R-CHOP demonstrated encouraging clinical efficacy and a safety profile consistent with the known toxicities of the individual drugs.

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The consortium on newborn screening in Africa for sickle cell disease: study rationale and methodology.

Effectiveness of these early interventions, along with culturally appropriate family education and counseling, will be evaluated by comparing U5 mortality in the enrolled cohort to estimated pre-program data. Here we describe the methodology planned for this trial.

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The impact of early PEG-asparaginase discontinuation in young adults with ALL: A post hoc analysis of the C10403 study.

In contrast, there was no impact of early PEG-asparaginase discontinuation on OS (P=0.64) or EFS (P=0.32) in patients with high-risk disease based on the presence of high-risk cytogenetics, Ph-like genotype, and/or high WBC at presentation. In conclusion, early PEG-asparaginase discontinuation is common in young adults with ALL and may adversely impact survival of patients with standard-risk ALL.

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Treatment of congenital thrombocytopenia and decreased collagen reactivity in G6b-B-deficient mice.

In contrast, treatment with the thrombopoietin mimetic romiplostim rescued thrombocytopenia, GPVI expression, and platelet reactivity to collagen, suggesting this may be a promising therapeutic for patients lacking functional G6b-B. Intriguingly, GPVI and a2ß1 expression are significantly downregulated in romiplostim-treated wild-type mice, whereas GPVI was upregulated in romiplostim-treated G6b KO mice, suggesting a cell intrinsic feedback mechanism that auto-regulates platelet reactivity, depending physiological needs.

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Haematologica

BCMA loss in the epoch of novel immunotherapy for multiple myeloma: from biology to clinical practice.

Therefore, strategies to overcome this kind of drug resistance are needed for these patients. In this review, we will discuss the loss of BCMA in the new epoch of immunotherapy for MM.

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Cytomegalovirus reactivation after CD19 CAR T cell therapy is clinically significant.

Not available.

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Enhancing regulatory T cell function via inhibition of high mobility group box 1 protein signaling in immune thrombocytopenia.

These results indicated that 18ß-GA has the potential to restore immune balance in ITP via inhibition of HMGB1 signaling. In short, this study reveals the role of HMGB1 in ITP, which may serve as a potential target for thrombocytopenia therapy.

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Pathology review identifies frequent misdiagnoses in recurrent classic Hodgkin lymphoma in a nation-wide cohort: Implications for clinical and epidemiological studies Authors.

Based on these data, risk to develop NHL after CHL treatment was re-calculated to 3.6-fold (standardized incidence ratio 3.61; CI 2.29-5.42). In addition, this study highlights the clinicopathological pitfalls leading to misinterpretation of CHL and consequences for individual patient care, interpretation of trials and epidemiological assessments.

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Prognostic value of positron emission tomography/computed tomography in transplanteligible newly diagnosed multiple myeloma patients from CASSIOPEIA: the CASSIOPET study.

Not available.

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The real risk of secondary non-Hodgkin lymphoma following Classical Hodgkin lymphoma.

Not available.

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Three-year results from phase 1 of ZUMA-4: KTE-X19 in pediatric relapsed/refractory acute lymphoblastic leukemia.

Pediatric/adolescent patients with R/R B-ALL achieved high MRD-negative remission rates with manageable safety profile after a single dose of KTE-X19. Phase 2 is ongoing at the 1×106 CAR T cells/kg (40 mL) dose.

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Treatment patterns and outcomes in relapsed/refractory follicular lymphoma: results from the international SCHOLAR-5 study.

Treatments were heterogenous at each LoT in both the US and Europe. Few FL patients achieved complete response in later LoT, and duration of response and survival diminished with each subsequent line.

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J Hematol Oncol

Efficacy and safety of CPX-351 versus 7+3 chemotherapy by European LeukemiaNet 2017 risk subgroups in older adults with newly diagnosed, high-risk/secondary AML: post hoc analysis of a randomized, phase 3 trial.

ClinicalTrials. gov Identifier: NCT01696084.

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Phase II trial of daratumumab with DCEP in relapsed/refractory multiple myeloma patients with extramedullary disease.

Except for the planned 30% dose adjustment in cycle 1, only 2 patients required DCEP dose reduction. This is one of the very few prospective trials focusing on EMD and we successfully laid grounds for implementing immunochemotherapy in MM treatment.

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Lancet Haematol

Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial.

Future randomised studies should evaluate the routine incorporation of blinatumomab in the treatment of patients with Ph-negative B-cell acute lymphocytic leukaemia. Funding Amgen.

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Leukemia

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes.

Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P<5×10 -8 ), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.

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METTL3 mediates chemoresistance by enhancing AML homing and engraftment via ITGA4.

Mechanistically, METTL3 extended the half-life of ITGA4 mRNA by m 6 A methylation, and then, increased expression of ITGA4 protein to enhance homing/engraftment of AML cells. The results provide insights into the function of m 6 A modification on the interaction between AML cells and BM niches and clarify the relationship between METTL3 and AML homing/engraftment, suggesting a therapeutic strategy for the treatment of refractory/relapsed AML with METTL3 inhibitors.

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Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia.

The burden of germline variants in BMF and MN was clearly associated with acquisition of monosomy 7. While BMF cases carrying germline variants showed similar overall survival as compared to the wild-type (WT) cases, MN cases with germline variants experienced a significantly shorter overall survival as compared to WT cases.

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Srsf2P95H/+ co-operates with loss of TET2 to promote myeloid bias and initiate a chronic myelomonocytic leukemia-like disease in mice.

We reproduce Srsf2/Tet2 co-operativity in vivo, yielding a disease with core characteristics of CMML, unlike single Srsf2 or Tet2 mutation. This model represents a significant step toward building high fidelity and genetically tractable models of CMML.

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Thromb Haemost

External validation of ACUITY/HORIZON bleeding risk score among acute coronary syndrome patients in Thai PCI Registry.

The ACUITY/HORIZON score was successfully validated in contemporary predictive and risk-adjustment models for PCI-related bleeding. The update models had good operating characteristics in patients from a real-world ACS population irrespective of bleeding definitions.

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Reviews&Editorials

Plenty of the editorials are available as full text through the publisher website using the provided link

Ann Oncol

Rules for the conduct of clinical trials need revision, but "good clinical practice" requires much more.

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Blood

Claiming the mantle of the brain.

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KMT2A-rearranged leukemia: the shapeshifter.

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J Hematol Oncol

Drugging KRAS: current perspectives and state-of-art review.

We also discuss the relationship between KRAS mutations and the tumour microenvironment, and therapeutic strategies to target KRAS. Finally, we review the current clinical evidence and ongoing clinical trials of novel agents targeting KRAS and shine light on resistance pathways known so far.

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Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy.

In this review, we summarize the emerging research on the function and underlying pathways of B7-H3, the expression and roles of B7-H3 in different cancer types, and the advances in B7-H3-targeted therapy. Considering different tumor microenvironment characteristics and results from preclinical models to clinical practice, the research indicates that B7-H3 is a promising target for future immunotherapy, which might eventually contribute to an improvement in cancer immunotherapy that will benefit patients.

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Leukemia

Central nervous system involvement in childhood acute lymphoblastic leukemia: challenges and solutions.

Fortunately, research into CNS-ALL is now making progress in addressing these unmet needs: biomarkers, such as CSF-flow cytometry, are now being tested in prospective trials, novel drugs are being tested in Phase I/II trials, and immunotherapies are increasingly available to patients with CNS relapses. The future is hopeful for improved management of the CNS over the next decade.

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Hyperdiploidy: the longest known, most prevalent, and most enigmatic form of acute lymphoblastic leukemia in children.

Irrespective of this underutilization, however, the detailed genetic characterization of HD leukemias may, especially in planned treatment reduction trials, eventually become important for further treatment stratification, patient management, and the clinical elucidation of outcome data. It should therefore become an integral part of al upcoming treatment studies.

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Miscellaneous

misc publications eg case reports, tools of the trade, images of the month, etc…

Blood

light chain-expressing hematogones in a patient with -restricted CLL and multiple myeloma on daratumumab therapy.

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Anticoagulation-associated AUB after VTE.

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Clonal hematopoiesis transcending species barriers.

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Connecting the dots: lenalidomide and t-MNs.

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Multiple myeloma presenting with extracellular crystal deposition in the bone marrow.

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Optimized CD19/CD22/CD3 antibody.

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Tackling ALK-positive LBCL.

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The burden of heavy menstrual bleeding.

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Blood Adv

Flow Cytometry as a fast, cost-effective tool to assess IgHV mutational status in CLL.

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Postibrutinib relapse outcomes for patients with marginal zone lymphoma.

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Treatment of primary mediastinal B-cell lymphoma with dose-adjusted REPOCH during pregnancy.

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Lancet Haematol

Blinatumomab plus hyper-CVAD: the prelude to a new era in acute lymphocytic leukaemia.

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COP27 Climate Change Conference: urgent action needed for Africa and the world.

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Leukemia

Central nervous system involvement in childhood acute lymphoblastic leukemia is linked to upregulation of cholesterol biosynthetic pathways.

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Clonal hematopoiesis is associated with hematological toxicity during lenalidomide-based therapy for MCL.

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Multi-hit TET2 mutations as a differential molecular signature of oligomonocytic and overt chronic myelomonocytic leukemia.

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Temporal changes of the incidence of childhood B-cell precursor acute lymphoblastic leukaemia in Germany during the COVID-19 pandemic.

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Letters&Replies

Letters to the editors and authors’ replies

Am J Hematol

Lineage switch from acute myeloid leukemia to B-lymphoblastic lymphoma with acquired PIK3R1 loss-of-function mutation.

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J Hematol Oncol

Direct identification of HLA class I and class II-restricted T cell epitopes in pancreatic cancer tissues by mass spectrometry.

T cell epitopes in PDAC can be discovered by the MS approach and can be designed into vaccine and TCR-T cell therapies for both HLA-type matched and non-matched patients.

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Randomized phase 2 trial of intravenous oncolytic virus JX-594 combined with low-dose cyclophosphamide in patients with advanced soft-tissue sarcoma.

Systemic treatment with JX-594 is safe in patients with advanced STS. Further investigations are needed to improve immune response to oncolytic viruses and define their therapeutic potential in patients with STS.

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Targeting ERRa promotes cytotoxic effects against acute myeloid leukemia through suppressing mitochondrial oxidative phosphorylation.

Single cell RNA-Seq analysis of human primary AML cells indicated that ERRa-expressing cancer cells had significantly higher mtOXPHOS enrichment scores. Blockade of ERRa by pharmacologic inhibitor (XCT-790) or gene silencing suppressed mtOXPHOS and increased anti-leukemic effects in vitro and in xenograft mouse models.

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Leukemia

Classification of rare pediatric myeloid neoplasia-Quo vadis?

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Finding consistency in classifications of myeloid neoplasms: a perspective on behalf of the International Workshop for Myelodysplastic Syndromes.

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SF3B1 mutations in AML are strongly associated with MECOM rearrangements and may be indicative of an MDS pre-phase.

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